Butyrate-Mediated Genomic Changes Involved in Non-Specific Host Defenses, Matrix Remodeling and the Immune Response in the Rumen Epithelium of Cows Afflicted With Subacute Ruminal Acidosis

Abstract

Subacute Ruminal Acidosis (SARA) is a disorder in cattle which can lead to chronic inflammation in the rumen epithelium, known as rumenitis. Butyrate has been shown to attenuate some of the detrimental effects of inflammatory gastroenteral disorders but the molecular mechanisms mediated by butyrate have not been defined. The objective of this study was to define the inflammatory-related genomic changes responsible for the beneficial effects of butyrate. Experimentally, 16 fistulated dairy cows at mid-lactation were fed a SARA-inducing (45% non-fiber carbohydrate) diet beginning 2 days before the beginning of treatment and continuing throughout the experiment. Cows were then evenly divided into treatment groups where a carrier with (n = 8) or without (n = 8) supplemental butyrate (2.5% initial DM intake) was deposited into the rumen daily for 7 days. The minimum rumen pH was higher in cows with supplemental butyrate (4.96±0.09 to 5.20±0.05, p = 0.040), but mean pH, maximum pH and the duration for which rumen pH was below 5.6 was unaffected. Free plasma Lipopolysaccharide (LPS) concentration was unaffected by treatment as was the concentration of Serum Amyloid A (SAA), although the LPS Binding Protein (LBP) concentration was increased by the addition of butyrate to the rumen (6.91±0.29 to 7.93±0.29 µg mL −1 , p = 0.024). Of the rumen Short Chain Fatty Acids (SCFA) tested, only butyrate showed a pronounced treatment effect, rising from 8.60±0.94 to 21.60±0.94 mM (p≤0.0001). Plasma Beta-Hydroxybutyrate (BHBA) concentration also increased (799.50±265.24 to 3261.63±265.24 µM, p≤0.001). Butyrate infusion did not affect milk parameters (total fat, lactose, total protein and LOS); however, when related to dry matter intake, milk production efficiency was increased (p = 0.035). Microarray and qRT-PCR analyses of rumen papillae biopsies collected on day 7 found that butyrate administration affected (p≤0.05) the expression of genes involved in Non-Specific Host Defense (NSHD), Remodeling or adaptation (RM) and Immune Response (IR). Of the 49 genes tested by qRT-PCR, 9 (LCN2, MMP1, MUC16, GPX2, CSTA, FUT1, SERPINE2, BCAM, RAC3) were upregulated, 20 (MTOR, AKIRIN2, NFKBIZ, NFKB2, ACVR2A, LAMB1, FRS2, PPARD, LBP, NEDD4L, SGK1, DEDD2, MAP3K8, PARD6B, PLIN2, ADA, HPGD, FMO5, BMP6, TCHH) were downregulated and 20 were unchanged due to butyrate administration in the proximal gastrointestinal tract. AJAVSThese results demonstrate the potential protective effect and molecular mechanisms involved in a novel butyrate treatment for inflammatory gastrointestinal conditions.

Transcriptomic Changes in Ruminal Tissue Induced by the Periparturient Transition in Dairy Cows

“…Indeed, our group has previously reported genomic changes related to cholesterol homeostasis in the rumen of dairy cattle (Steele et al, 2011b). Moreover, we recently reported that major structural changes in the rumen are facilitated by components of the immune system (Dionissopoulos et al, 2013). In order to help better understand the physiological changes that take place during the peripartal period, changes in gene expression of key nutrient metabolic pathways should be elucidated.…”

BUTYRATE SUPPLEMENTATION AFFECTS mRNA ABUNDANCE OF GENES INVOLVED IN GLYCOLYSIS, OXIDATIVE PHOSPHORYLATION AND LIPOGENESIS IN THE RUMEN EPITHELIUM OF HOLSTEIN DAIRY COWS

“…Butyrate concentrations on both days 1 and 7 were higher in butyrate than in control (22.60±0.94 Vs 9.88±0.94 mM and 21.60±0.94 Vs 8.60±0.94 mM; Dionissopoulos et al, 2013). Serum BHBA was higher in the butyrate treatment than the control treatment on both days 1 (4201±265 Vs 910±265 µM) and 7 (3262±265 Vs 800±265 µM; Dionissopoulos et al, 2013).…”

“…Butyrate concentrations on both days 1 and 7 were higher in butyrate than in control (22.60±0.94 Vs 9.88±0.94 mM and 21.60±0.94 Vs 8.60±0.94 mM; Dionissopoulos et al, 2013). Serum BHBA was higher in the butyrate treatment than the control treatment on both days 1 (4201±265 Vs 910±265 µM) and 7 (3262±265 Vs 800±265 µM; Dionissopoulos et al, 2013). Rumen pH measurements confirmed the occurrence of acidosis in both butyrate and control treatments, as indicated by the time rumen pH was less than 5.6 (536±89 and 598±97 min/day, respectively; Dionissopoulos et al, 2013).…”

“…This study was carried out as described previously (Dionissopoulos et al, 2013). All animal procedures were approved by the Animal Care Committee at the University of Guelph under the guidelines of the Canadian Council for Animal Care (Ottawa, ON, CA).…”

“…Rumen papillae samples were analyzed by microarray as previously described (Dionissopoulos et al, 2013). Samples from the control treatment were pooled and the butyrate samples were compared to the pooled control samples using student's t-test (Xue et al, 2010).…”